The board objectives of this project are to study the different mechanisms of pyrimidine nucleotide biosynthesis involved in cellular proliferation utilizing normal and neoplastic colon. These objectives are being pursued by measurement of enzymes of de novo and salvage pathways of pyrimidine biosynthesis, by measurement of incorporation of radioactive precursors into pyrimidine nucleotides, by measurement of factors important in the regulation of pyrimidine biosynthesis and by measurement of inhibitors of pyrimidine biosynthesis and the effect on cellular proliferation in normal and neoplastic colon. These studies are to be carried out in colonic tissues removed from control mice and mice injected with dimethylhydrazine (to induce colonic cancer) and in tissue-culture cells established from colonic tissue.